Condition category
Nervous System Diseases
Date applied
25/03/2009
Date assigned
08/05/2009
Last edited
25/01/2012
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Peter N Leigh

ORCID ID

Contact details

Academic Neurosciences Centre
PO41 Institute of Psychiatry
King's College London
London
SE5 8AF
United Kingdom

Additional identifiers

EudraCT number

2008-006891-31

ClinicalTrials.gov number

Protocol/serial number

RAA/2008/013

Study information

Scientific title

A double-blind randomised controlled trial of Lithium Carbonate in patients with Amyotrophic Lateral Sclerosis

Acronym

LiCALS

Study hypothesis

Lithium carbonate, combined with standard amyotrophic lateral sclerosis (ALS) treatment, may prolong survival, slow the rate of functional deterioration and improve the quality of life and mental state of ALS patients, measured over 18 months.

Ethics approval

South East Research Ethics Committee gave approval on the 17th February 2009 (ref: 09/H1102/15)

Study design

Multicentre double-blind randomised parallel group controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Amyotrophic lateral sclerosis (ALS); also known as motor neurone disease (MND)

Intervention

Lithium carbonate or matched placebo.

The dose will be titrated during the first 4 weeks of the trial (some patients may require a longer titration period) to achieve plasma lithium levels of 0.4 - 0.8 mmol/l. Tablets will be given orally once a day (in the evening). The tablets contain 295 mg of lithium carbonate or placebo - we anticipate that most patients will be on two tablets for the duration of the trial, following the titration phase. Some people may need three tablets or, in exceptional circumstances, four.

The total duration of treatment (and follow-up) is 18 months (77 weeks).

Intervention type

Drug

Phase

Phase IV

Drug names

Lithium carbonate

Primary outcome measures

Death from any cause at 18 months defined from the date of randomisation

Secondary outcome measures

1. Slope of ALS Functional Rating Scale - Revised (ALSFRS-R) scores
2. Change in EuroQOL (EQ-5D)
3. Change in Hospital Anxiety and Depression Scale (HADS)

Collected at week 0 (baseline), week 12 (month 3), month 6, 9, 2, 15 and 18 (and withdrawal).

Overall trial start date

01/05/2009

Overall trial end date

01/03/2012

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients with possible, laboratory-supported probable, probable or definite ALS according to the revised version of the El Escorial World Federation of Neurology criteria (The Airlie House Statement: http://www.wfnals.org). These criteria are internationally accepted research diagnostic criteria with high specificity and sensitivity. The onset form (bulbar or limb) and disease type (familial or sporadic) will be recorded; source documents will include a full report of an electromyogram (EMG) reported by an experienced neurophysiologist as compatible with ALS. The neurological exam should be performed by a physician.
2. Disease duration greater than or equal to 6 months and less than or equal to 36 calendar months (inclusive), with disease onset defined as date of first muscle weakness, or dysarthria
3. SVC greater than or equal to 60% of predicted within 1 month prior to randomisation
4. Aged greater than or equal to 18 years (inclusive), either sex
5. In the case of a female with childbearing potential, the patient must not be pregnant or breast-feeding. Women of childbearing potential will have a urine pregnancy test before randomisation and at each clinic visit. The results of those must be negative. Women of childbearing potential should use adequate contraception.
6. Continuously treated with riluzole for at least 4 weeks prior to screening (28 days inclusive) and stabilised at 100 mg/day (50 mg twice daily [bid]) without significant adverse drug reactions
7. Capable of understanding the information given and giving fully informed consent prior to any study specific procedures

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

220

Participant exclusion criteria

1. Participation in another therapeutic study within the preceding 12 weeks or use of other investigational drugs or agents
2. Tracheostomy, or assisted ventilation of any type during the preceding three months
3. Existing gastrostomy, unless elective and not currently used for nutritional support or hydration
4. Any medical condition known to have an association with motor neuron dysfunction which might confound or obscure the diagnosis of ALS
5. Presence of any concomitant life-threatening disease or any disease or impairment likely to interfere with functional assessment
6. Confirmed hepatic insufficiency or abnormal liver function (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] greater than 1.5 times the upper limit of the normal range) within one month of randomisation. That blood test may be repeated in the case of initial abnormal results; if the levels return to normal, the patient may then be included in the study.
7. Renal insufficiency (serum creatinine greater than upper limit of normal [ULN] for the centre/local laboratory) within one month of randomisation. That blood test may be repeated in the case of initial abnormal results; if the level returns to normal, the patient may then be included in the study.
8. Recorded diagnosis or evidence of major psychiatric disorder or clinically evident dementia
9. Known allergy or hypersensitivity to lithium, or its excipients
10. Likely to be uncooperative or to fail to comply with the trial requirements or to be inaccessible in the event of an emergency
11. Subjects with significant haematological, biochemical and autoimmune abnormalities, as judged by the study physician
12. If a woman of childbearing potential, unable or unwilling to use effective contraception during the study
13. Patients with active inflammation/infection at screening or baseline (day 0). Patients presenting with active inflammation/infection can be reassessed at a later date, and included in the trial if the infection/inflammation has cleared.
14. Patients already taking lithium in any form
15. Presence of a medical condition contra-indicative to the use of lithium, according to the British National Formulary (BNF) (http://www.bnf.org/bnf/)

Recruitment start date

01/05/2009

Recruitment end date

01/03/2012

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Academic Neurosciences Centre
London
SE5 8AF
United Kingdom

Sponsor information

Organisation

King's College London (UK)

Sponsor details

PO01
Institute of Psychiatry
De Crespigny Park
London
SE5 8AF
United Kingdom

Sponsor type

University/education

Website

http://www.iop.kcl.ac.uk/

Funders

Funder type

Charity

Funder name

Motor Neurone Disease (MND) Association (UK) (ref: Leigh/Jul08/RF/6345)

Alternative name(s)

MNDA

Funding Body Type

private sector organisation

Funding Body Subtype

professional associations and societies

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2011 protocol in http://www.ncbi.nlm.nih.gov/pubmed/21936930

Publication citations

  1. Protocol

    Al-Chalabi A, Shaw PJ, Young CA, Morrison KE, Murphy C, Thornhill M, Kelly J, Steen IN, Leigh PN, , Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic lateral sclerosis (LiCALS) [Eudract number: 2008-006891-31]., BMC Neurol, 2011, 11, 111, doi: 10.1186/1471-2377-11-111.

Additional files

Editorial Notes